Zusammenfassung:
Kopf-Hals-Tumore (HNSCC) können durch die klassischen Noxen Tabak und Alkohol aber auch durch eine Infektion mit dem humanen Papillomavirus induziert werden. Die zweite Gruppe stellt eine eigene Tumorentität dar mit bevorzugter Lokalisation im Oropharynx. Während HNSCC-Tumore weltweit rückläufig sind, steigt die Zahl HPV-assoziierter Tumore in Europa, Japan und den USA deutlich an. Diese Patienten sind in der Regel jünger und haben weniger Begleiterkrankungen, vor allem aber zeigen sie nach Radiochemotherapie eine deutlich bessere Prognose.
Daten des The Cancer Genome Atlas (TCGA) zeigen, dass diese beiden Tumorentitäten sich offensichtlich nicht bezüglich Mutationslast oder Veränderung der Kopienzahl von Chromosomen unterscheiden, wohl aber in der Genexpression.
Ziel der vorliegenden Arbeit war es, erstmalig anhand von jeweils fünf Zelllinien zu überprüfen, inwieweit sich HPV-negative und -positive Zellen bezüglich DNA-Gehalt sowie numerischer und struktureller Chromosomenaberrationen unterscheiden. Der DNA-Gehalt wurde mittels Flusszytometrie und die numerischen und strukturellen Aberrationen mittels G-Banden-gefärbten Metaphase-Präparaten bzw. m-FISH geprüft.
Für beide Entitäten wird sowohl im DNA-Gehalt als auch in der Zahl der Chromosomen eine große Variation gefunden, wobei diese beiden Parameter eng miteinander korrelieren. Im Mittel besteht allerdings sowohl bezüglich DNA-Gehalt als auch Zahl der Chromosomen kein signifikanter Unterschied zwischen HPV-negativen und –positiven HNSCC-Zelllinien.
Die Aneuploidie, wie sie mittels m-FISH für jedes Chromosom bestimmt wurde, zeigte je nach Chromosom eine große Variation zwischen diploidem, triploidem und tetraploidem Status. Besonders erstaunlich ist, dass bis auf Chromosom 7 diese Variation für HPV-negative und HPV-positive Zelllinien nahezu identisch ist. Diese Variation stimmte zudem mit den beiden einzigen bisher veröffentlichen Datensätzen überein. Daher wird für diese Variation bei HNSCC-Zellen von einer Gesetzmäßigkeit auszugegangen, die zudem unabhängig vom HPV-Status ist.
Der Nachweis der strukturellen Chromosomenaberration zeigte für HPV-negative Zelllinien insgesamt ein sehr heterogenes Bild, während für HPV-positive Linien eine besondere Präferenz für die Chromosomen 2, 3 und 5 beobachtet wird. Insbesondere für Chromosom 3 wurden für HPV-positive Zellen signifikant mehr Translokationen nachgewiesen als für HPV-negative Linien. Es wird vermutet, dass in der chromosomalen Instabilität dieser Region die Ursache für die höhere Radiochemieempfindlichkeit HPV-positiver Tumore begründet ist.
Bibliographie / References
- Glenny A-M, Furness S, Worthington HV, Conway DI, Oliver R, Clarkson JE, et al. Interventions for the treatment of oral cavity and oropharyngeal cancer: Radiotherapy. Cochrane Database Syst Rev. 2010(12):CD006387. doi:10.1002/14651858.CD006387.pub2.
- van Kempen PMW, Noorlag R, Braunius WW, Moelans CB, Rifi W, Savola S, et al. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma. Cancer Med. 2015;4(10):1525-35. doi:10.1002/cam4.499.
- Urban D, Corry J, Rischin D. What is the best treatment for patients with human papillomavirus-positive and -negative oropharyngeal cancer? Cancer. 2014;120(10):1462-70. doi:10.1002/cncr.28595.
- Zhang D-H, Chen J-Y, Hong C-Q, Yi D-Q, Wang F, Cui W. High-risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis. Cancer. 2014;120(17):2673-83. doi:10.1002/cncr.28797.
- Watson JV, Chambers SH, Smith PJ. A pragmatic approach to the analysis of DNA histograms with a definable G1 peak. Cytometry. 1987;8(1):1-8. doi:10.1002/cyto.990080101.
- Microcell-mediated transfer of chromosome 4 into HeLa cells suppresses telomerase activity. Genes Chromosomes Cancer. 2001;31(2):196-8. doi:10.1002/gcc.1134.
- Reshmi SC, Saunders WS, Kudla DM, Ragin CR, Gollin SM. Chromosomal instability and marker chromosome evolution in oral squamous cell carcinoma. Genes Chromosomes Cancer. 2004;41(1):38-46. doi:10.1002/gcc.20064.
- Gollin SM. Cytogenetic alterations and their molecular genetic correlates in head and neck squamous cell carcinoma: A next generation window to the biology of disease. Genes Chromosomes Cancer. 2014;53(12):972-90. doi:10.1002/gcc.22214.
- Dahlgren L, Mellin H, Wangsa D, Heselmeyer-Haddad K, Bjrnestl L, Lindholm J, et al. Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus-positive and - negative tumors. Int J Cancer. 2003;107(2):244-9. doi:10.1002/ijc.11371.
- Nsman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009;125(2):362-6. doi:10.1002/ijc.24339.
- Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893- 917. doi:10.1002/ijc.25516.
- Sethi S, Ali-Fehmi R, Franceschi S, Struijk L, van Doorn L-J, Quint W, et al. Characteristics and survival of head and neck cancer by HPV status: A cancer registry-based study. Int J Cancer. 2012;131(5):1179-86. doi:10.1002/ijc.26500.
- Dietz A, Wichmann G, Wiegand S. Should We De-escalate the Treatment for HPV- Positive Tumors? Recent Results Cancer Res. 2017;206:173-81. doi:10.1007/978- 3-319-43580-0_13.
- Arenz A, Ziemann F, Mayer C, Wittig A, Dreffke K, Preising S, et al. Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis. Strahlenther Onkol. 2014;190(9):839-46. doi:10.1007/s00066-014-0605-5.
- Wagner S, Wrdemann N, Hbbers C, Reuschenbach M, Prigge E-S, Wichmann G, et al. HPV-assoziierte Kopf-Hals-Karzinome: Mutationssignaturen und genomische Aberrationen. HNO. 2015;63(11):758-67. doi:10.1007/s00106-015-0074-x.
- Humane Papillomviren bei Plattenepithelkarzinomen der Kopf-und Halsregion: Relevanz fr Prognose, Therapie und Prophylaxe. HNO. 2016;64(7):450-9. doi:10.1007/s00106-016-0123-0.
- Knecht R, Bussmann L, Mckelmann N, Lrincz BB. Ist Radio(chemo)therapie wirklich der zuknftige Standard fr die Behandlung von Oropharynxkarzinomen? HNO. 2016;64(4):221-6. doi:10.1007/s00106-016-0147-5.
- Agaimy A, Weichert W. Grading von Tumoren der Kopf-Hals-Region. Pathologe. 2016;37(4):285-92. doi:10.1007/s00292-016-0173-9.
- Rautava J, Syrjnen S. Biology of human papillomavirus infections in head and neck carcinogenesis. Head Neck Pathol. 2012;6 Suppl 1:S3-15. doi:10.1007/s12105- 012-0367-2.
- Hess J, Unger K, Orth M, Schtz U, Schttrumpf L, Zangen V, et al. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance. Cancer Lett. 2017;386:87-99. doi:10.1016/j.canlet.2016.11.014.
- Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646-74. doi:10.1016/j.cell.2011.02.013.
- Thompson SL, Bakhoum SF, Compton DA. Mechanisms of chromosomal instability. Curr Biol. 2010;20(6):R285-95. doi:10.1016/j.cub.2010.01.034.
- Nygrd M, Aagnes B, Bray F, Mller B, Mork J. Population-based evidence of increased survival in human papillomavirus-related head and neck cancer. Eur J Cancer. 2012;48(9):1341-6. doi:10.1016/j.ejca.2012.03.014.
- Tinhofer I, Jhrens K, Keilholz U, Kaufmann A, Lehmann A, Weichert W, et al. Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence. Eur J Cancer. 2015;51(4):514-21. doi:10.1016/j.ejca.2014.12.018.
- Conway C, Chalkley R, High A, Maclennan K, Berri S, Chengot P, et al. Next- generation sequencing for simultaneous determination of human papillomavirus load, subtype, and associated genomic copy number changes in tumors. J Mol Diagn. 2012;14(2):104-11. doi:10.1016/j.jmoldx.2011.10.003.
- White JS, Weissfeld JL, Ragin CCR, Rossie KM, Martin CL, Shuster M, et al. The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol. 2007;43(7):701-12. doi:10.1016/j.oraloncology.2006.09.001.
- Simard EP, Torre LA, Jemal A. International trends in head and neck cancer incidence rates: Differences by country, sex and anatomic site. Oral Oncol. 2014;50(5):387- 403. doi:10.1016/j.oraloncology.2014.01.016.
- Sher DJ, Adelstein DJ, Bajaj GK, Brizel DM, Cohen EEW, Halthore A, et al. Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline. Pract Radiat Oncol. 2017;7(4):246-53. doi:10.1016/j.prro.2017.02.002.
- Rieckmann T, Tribius S, Grob TJ, Meyer F, Busch C-J, Petersen C, et al. HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol. 2013;107(2):242-6. doi:10.1016/j.radonc.2013.03.013.
- Geigl JB, Obenauf AC, Schwarzbraun T, Speicher MR. Defining 'chromosomal instability'. Trends Genet. 2008;24(2):64-9. doi:10.1016/j.tig.2007.11.006.
- Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA. The biology and life-cycle of human papillomaviruses. Vaccine. 2012;30 Suppl 5:F55-70. doi:10.1016/j.vaccine.2012.06.083.
- Bhide SA, Thway K, Lee J, Wong K, Clarke P, Newbold KL, et al. Delayed DNA double-strand break repair following platin-based chemotherapy predicts treatment response in head and neck squamous cell carcinoma. Br J Cancer. 2016;115(7):825-30. doi:10.1038/bjc.2016.266.
- Lawrence MS and The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576-82. doi:10.1038/nature14129.
- Speicher MR, Gwyn Ballard S, Ward DC. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet. 1996;12(4):368-75. doi:10.1038/ng0496-368.
- Albertson DG, Collins C, McCormick F, Gray JW. Chromosome aberrations in solid tumors. Nat Genet. 2003;34(4):369-76. doi:10.1038/ng1215.
- Moody CA, Laimins LA. Human papillomavirus oncoproteins: Pathways to transformation. Nat Rev Cancer. 2010;10(8):550-60. doi:10.1038/nrc2886.
- Duensing S, Mnger K. Human papillomaviruses and centrosome duplication errors: Modeling the origins of genomic instability. Oncogene. 2002;21(40):6241-8. doi:10.1038/sj.onc.1205709.
- Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567-78. doi:10.1056/NEJMoa053422.
- Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tn PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217.
- Multiplex-FISH for pre-and postnatal diagnostic applications. Am J Hum Genet. 1999;65(2):448-62. doi:10.1086/302508.
- Lee C, Gisselsson D, Jin C, Nordgren A, Ferguson DO, Blennow E, et al. Limitations of chromosome classification by multicolor karyotyping. Am J Hum Genet. 2001;68(4):1043-7. doi:10.1086/319503.
- Das LC, Karrison TG, Witt ME, Muller C, Stenson K, Blair EA, et al. Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal squamous cell carcinoma over two decades. Ann Oncol. 2015;26(1):198-205. doi:10.1093/annonc/mdu511.
- Marullo R, Werner E, Zhang H, Chen GZ, Shin DM, Doetsch PW. HPV16 E6 and E7 proteins induce a chronic oxidative stress response via NOX2 that causes genomic instability and increased susceptibility to DNA damage in head and neck cancer cells. Carcinogenesis. 2015;36(11):1397-406. doi:10.1093/carcin/bgv126.
- Jalal SM, Law ME. Utility of multicolor fluorescent in situ hybridization in clinical cytogenetics. Genet Med. 1999;1(5):181-6. doi:10.1097/00125817-199907000- 00003.
- Rhie A, Park WS, Choi MK, Kim J-H, Ryu J, Ryu CH, et al. Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection. Medicine (Baltimore). 2015;94(50):e2187. doi:10.1097/MD.0000000000002187.
- Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154-7. doi:10.1126/science.1206923.
- Tungteakkhun SS, Filippova M, Fodor N, Duerksen-Hughes PJ. The full-length isoform of human papillomavirus 16 E6 and its splice variant E6* bind to different sites on the procaspase 8 death effector domain. J Virol. 2010;84(3):1453-63. doi:10.1128/JVI.01331-09.
- Thibaudeau E, Fortin B, Coutle F, Nguyen-Tan P, Weng X, Audet M-L, et al. HPV Prevalence and Prognostic Value in a Prospective Cohort of 255 Patients with Locally Advanced HNSCC: A Single-Centre Experience. Int J Otolaryngol. 2013;2013:437815. doi:10.1155/2013/437815.
- Kimple RJ, Smith MA, Blitzer GC, Torres AD, Martin JA, Yang RZ, et al. Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res. 2013;73(15):4791-800. doi:10.1158/0008-5472.CAN-13-0587.
- Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467-75. doi:10.1158/1055-9965.EPI-04- 0551.
- Klussmann JP, Mooren JJ, Lehnen M, Claessen SMH, Stenner M, Huebbers CU, et al. Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res. 2009;15(5):1779-86. doi:10.1158/1078-0432.CCR-08-1463.
- Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015;21(3):632-41. doi:10.1158/1078-0432.CCR-13-3310.
- Jou A, Hess J. Epidemiology and Molecular Biology of Head and Neck Cancer. Oncol Res Treat. 2017;40(6):328-32. doi:10.1159/000477127.
- Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27(12):1992-8. doi:10.1200/JCO.2008.20.2853.
- Martins RG, Parvathaneni U, Bauman JE, Sharma AK, Raez LE, Papagikos MA, et al. Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: A randomized phase II trial. J Clin Oncol. 2013;31(11):1415-21. doi:10.1200/JCO.2012.46.3299.
- Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015;33(29):3235-42. doi:10.1200/JCO.2015.61.6995.
- Hayes DN, van Waes C, Seiwert TY. Genetic Landscape of Human Papillomavirus- Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors. J Clin Oncol. 2015;33(29):3227-34. doi:10.1200/JCO.2015.62.1086.
- Martin D, Abba MC, Molinolo AA, Vitale-Cross L, Wang Z, Zaida M, et al. The head and neck cancer cell oncogenome: A platform for the development of precision molecular therapies. Oncotarget. 2014;5(19):8906-23. doi:10.18632/oncotarget.2417.
- Wittekindt C, Wagner S, Mayer CS, Klussmann JP. Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2012;11:Doc09. doi:10.3205/cto000091.
- Wolff K-D, Follmann M, Nast A. The diagnosis and treatment of oral cavity cancer. Dtsch Arztebl Int. 2012;109(48):829-35. doi:10.3238/arztebl.2012.0829.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71-96. doi:10.3322/CA.2007.0010.
- Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. doi:10.3322/caac.20107.
- Albers AE, Grabow R, Qian X, Jumah MD, Hofmann VM, Krannich A, Pecher G. Efficacy and toxicity of docetaxel combination chemotherapy for advanced squamous cell cancer of the head and neck. Mol Clin Oncol. 2017;7(1):151-7. doi:10.3892/mco.2017.1281.
- Friedman JM, Stavas MJ, Cmelak AJ. Clinical and scientific impact of human papillomavirus on head and neck cancer. World J Clin Oncol. 2014;5(4):781-91. doi:10.5306/wjco.v5.i4.781.
- Hay RKM, Park J-G, Gazdar A. Atlas of Human Tumor Cell Lines. Burlington: Elsevier Science; 1994.
- Blaisdell JO, Harrison L, Wallace SS. Base excision repair processing of radiation- induced clustered DNA lesions. Radiat Prot Dosimetry. 2001;97(1):25-31.
- Heo DS, Snyderman C, Gollin SM, Pan S, Walker E, Deka R, et al. Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines. Cancer Res. 1989;49(18):5167-75.
- Vitre BD, Cleveland DW. Centrosomes, chromosome instability (CIN) and aneuploidy.
- Worsham MJ, Wolman SR, Carey TE, Zarbo RJ, Benninger MS, van Dyke DL. Chromosomal aberrations identified in culture of squamous carcinomas are confirmed by fluorescence in situ hybridisation. MP, Mol Pathol. 1999;52(1):42-6.
- Oda D, Bigler L, Mao EJ, Disteche CM. Chromosomal abnormalities in HPV-16- immortalized oral epithelial cells. Carcinogenesis. 1996;17(9):2003-8.
- Castleman KR, Eils R, Morrison L, Piper J, Saracoglu K, Schulze MA, Speicher MR. Classification accuracy in multiple color fluorescence imaging microscopy. Cytometry. 2000;41(2):139-47.
- Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res. 2003;9(11):4227-39.
- Sreekantaiah C, Rao PH, Xu L, Sacks PG, Schantz SP, Chaganti RS. Consistent chromosomal losses in head and neck squamous cell carcinoma cell lines. Genes Chromosomes Cancer. 1994;11(1):29-39.
- Fu YS, Reagan JW, Richart RM. Definition of precursors. Gynecol Oncol. 1981;12(2 Pt 2):S220-31.
- Ball H, Koldovsky P, Hoffmann T, Balz V, Hildebrandt B, Gerharz CD, Bier H. Establishment and characterization of four cell lines derived from human head and neck squamous cell carcinomas for an autologous tumor-fibroblast in vitro model.
- Braakhuis BJM, Snijders PJF, Keune W-JH, Meijer CJLM, Ruijter-Schippers HJ, Leemans CR, Brakenhoff RH. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004;96(13):998-1006.
- Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus.
- Lenarz T, Boenninghaus H-G. Hals-Nasen-Ohren-Heilkunde: Mit 6 Tabellen ; [mit Fallquiz]. 14th ed. Berlin: Springer; 2012.
- Lin CJ, Grandis JR, Carey TE, Gollin SM, Whiteside TL, Koch WM, Ferris RL. Head and neck squamous cell carcinoma cell lines: established models and rationale for selection. Head Neck. 2007;29(2):163-88.
- Lansford CD, Grenman R, Bier H, Somers KD, Kim SY, Whiteside TL, et al., editors. Human Cell Culture: Cancer Cell Lines Part 2 // Head and Neck Cancers. Dordrecht: Springer Netherlands; 2002.
- Guan XY, Meltzer PS, Dalton WS, Trent JM. Identification of cryptic sites of DNA sequence amplification in human breast cancer by chromosome microdissection.
- Ziemann F, Arenz A, Preising S, Wittekindt C, Klussmann JP, Engenhart-Cabillic R, Wittig A. Increased sensitivity of HPV-positive head and neck cancer cell lines to x- irradiation Cisplatin due to decreased expression of E6 and E7 oncoproteins and enhanced apoptosis. Am J Cancer Res. 2015;5(3):1017-31.
- Budach W, Blke E, Kammers K, Gerber PA, Orth K, Gripp S, Matuschek C. Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials.
- Steenbergen R, Hermsen M. Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line. Cancer Res. 1995:5465-71.
- Chao KS, Majhail N, Huang CJ, Simpson JR, Perez CA, Haughey B, Spector G. Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: A comparison with conventional techniques. Radiother Oncol. 2001;61(3):275-80.
- Saxon PJ, Srivatsan ES, Stanbridge EJ. Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J. 1986;5(13):3461-6.
- Grenman R, Carey TE, McClatchey KD, Wagner JG, Pekkola-Heino K, Schwartz D. In Vitro radiation resistance among cell lines established from patients with squamous cell carcinoma of the head and neck. Cancer. 1991;67(11):2471-7.
- Jin Y, Mertens F, Jin C, Akervall J, Wennerberg J, Gorunova L, et al. Nonrandom chromosome abnormalities in short-term cultured primary squamous cell carcinomas of the head and neck. Cancer Res. 1995;55(14):3204-10.
- Tang AL, Hauff SJ, Owen JH, Graham MP, Czerwinski MJ, Park JJ, Walline H. UM- SCC-104: a new human papillomavirus-16-positive cancer stem cell-containing head and neck squamous cell carcinoma cell line. Head Neck. 2012;34(10):1480- 91.